Recent advances in stem cell biology have enabled the generation of kidney organoids vitro, and further maturation these is observed after experimental transplantation. However, current remain immature their precise stages are difficult to determine because limited information on developmental stage-dependent gene expressions vivo. To establish relevant molecular coordinates, we performed singl...

Our understanding of the intrinsic effects of cystic fibrosis (CF) transmembrane conductance regulator (cftr) deletion on resident neonatal alveolar macrophage (AM) remains limited. We previously demonstrated that diminished glutathione (GSH) or excessive AM transforming growth factor beta one (TGFβ1) contributes to AM dysfunction in a variety of disease states. In this study, using a gut-corre...

Astrocytes are implicated in the neuropathology of Alzheimer’s disease (AD) by clustering with other activated inflammatory cells at the sites of amyloid beta (Aβ) deposits formed in the cortex and hippocampus. Astrocytes are known to contribute to the clearance of Aβ in the AD brain. Also, adult but not neonatal mouse astrocytes are able to clear Aβ deposits from the tissue sections of transge...

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca(2+)-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension i...

Immunological memory, which protects organisms from re-infection, is a hallmark of the mammalian adaptive immune system and the underlying principle of vaccination. In early life, however, mice and other mammals are deficient at generating memory CD8+ T cells, which protect organisms from intracellular pathogens. The molecular basis that differentiates adult and neonatal CD8+ T cells is unknown...

Neonatal mice with cystic fibrosis (CF) exhibit a very high mortality due to intestinal obstruction localized primarily to the ileum and colon. It has been hypothesized that lack of Cl- secretion and possibly elevated Na+ absorption contribute to the gut problems in CF neonates. Therefore, intestines (ileum, proximal colon, and distal colon) from normal and CF day-old mouse pups were studied on...

Pten deletion from adult mouse hematopoietic cells activates the PI3-kinase pathway, inducing hematopoietic stem cell (HSC) proliferation, HSC depletion, and leukemogenesis. Pten is also mutated in human leukemias, but rarely in early childhood leukemias. We hypothesized that this reflects developmental changes in PI3-kinase pathway regulation. Here we show that Rictor deletion prevents leukemo...

Neonatal diabetes mellitus is a rare condition, the causes of which are mostly unknown. One well defined though very rare entity is the autosomal recessive Wolcott-Rallison syndrome, in which permanent neonatal diabetes, osteopenia, and epiphyseal dysplasia occur. Only five previous families have been reported, and here we describe the second in which parental consanguinity was present. The pro...

Crigler-Najjar syndrome type I (CNSI) is a rare monogenic disease characterized by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of neurological damage and death. Liver transplantation is the only curative option, which has several limitations and risks. We applied an in vivo gene targeting approach based on the insertion, without the use of nucleases, of a promoterless t...

In contrast to adults, the murine neonatal CD4+ compartment contains a high frequency of recent thymic emigrants (RTEs). However, the functional capabilities of these cells in neonates are relatively unknown. Moreover, it has not been determined whether RTEs from neonates and adults are comparable. Here we have directly compared neonatal and adult CD4+ RTEs for the first time, using a transgeni...